Nano Biomedicine
ORIGINAL ARTICLE
 Cellular Response to ZnO Nanoparticle Toxicity Inferred from Global Gene Expression Profiles

 Nobutaka HANAGATA1,2,3, Mingsheng XU4,5, Taro TAKEMURA1, and Fei ZHUANG3

1Nanotechnology Innovation Center, National Institute for Materials Science, Ibaraki, Japan
2Biomaterials Center, National Institute for Materials Science, Ibaraki, Japan
3Graduate School of Life Science, Hokkaido University, Sapporo, Japan
4MOE Key Laboratory of Macromolecule Synthesis and Functionalization,
State Key Laboratory of Silicon Materials, and Department of
Polymer Science and Engineering, Zheijian University, Hangzhou, P.R.Cjina
5International Center for Young Scientists, National Institute for Materials Science, Ibaraki, Japan
Nano Biomedicine 2010;2(2): 153-169, (Dec 30)
Synopsis
We compared cytotoxicities of metal oxide nanomaterials, including different sizes (20 and 60 nm) of ZnO nanoparticles (NPs), Al-doped ZnO-NPs, Al2O3-NPs, Al2O3 nanowhiskers (NWs) and SiO2-NPs, on the basis of viabilities of human lung epithelial A549 cells exposed to these nanomaterials. Al2O3-NPs, Al2O3-NWs and SiO2-NPs showed no significant cytotoxic effects on viability. On the other hand, ZnO-NPs, which included ZnO-NPs (20 nm), ZnO-NPs (60 nm), and Al-doped ZnO-NPs, all showed toxic effects; however, no significant differences in cytotoxicity were observed among these ZnO-NPs, suggesting that nanoparticle size and Al-doping do not contribute to cytotoxicity. Global gene expression analysis using a DNA microarray revealed that 22 and 8 genes were consistently up- and down-regulated, respectively, in cells exposed to the 3 ZnO-NPs. Our results suggest that up-regulation of genes by ZnO-NPs leads to maintenance of zinc homeostasis and protection against oxidative stress, while down-regulation of genes causes disruption of zinc homeostasis, DNA damage, and apoptosis. The balance between protective mechanisms induced by up-regulated genes and cellular damages induced by down-regulated genes may determine the fate of cells.

Key words: ZnO nanoparticles, toxicity, lung epithelial cells, global gene expression

Supplementary Tables 1?6

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